Cannabis Chemistry and Ambivalent Effects

The chemistry of cannabis

The chemistry of cannabis is complex; the number of identified constituent compounds in the cannabis plant continues to grow almost annually. A recent analysis (ElSohly and Gul 2016:4) identifies 545 known compounds in Cannabis sativa; this includes flavonoids, terpenoids and 104 cannabinoids.

Eight kinds of CBDs (cannabidiols) and twenty kinds of THCs (tetra-hydrocannabinols) have now been identified. Eighteen types of Δ-9 THC and two types of Δ-8 THC are responsible for most of the psychoactive effects of cannabis. THCV is particularly interesting for its psychoactive properties (see my blog on ‘Various Preparations of Cannabis’).

Besides CBDs and THCs, there is a growing interest in the effect of other constituent non-psychoactive compounds in cannabis. Evidence is mounting that these other compounds may synergistically affect the activity of other psychoactive compounds, in particular the THCs. Raphael Mechoulam, the Israeli scientist who in 1963 was the first to isolate THC in cannabis, refers to this as the ‘entourage’ effect.

The terpenoids in the plant, which along with flavonoids also provide various odours and flavours, appear to synergistically assist the activation of the CBDs and THCs. Some flavonoids are strongly antioxidant and at least two of them are found uniquely in cannabis, one of which appears to have anti-inflammatory potential (Russo 2007:1618). One of the terpenoids, beta-caryophyllene, directly activates CB2 (Lee 2012:366), which is one of the two main receptor sites in the brain—the other being CB1—activated by cannabis.

Cannabigerol (CBG) and Cannabinol (CBN) are also being researched. CBG is non-psychoactive but binds to the CB1 and CB2 receptor sites in the brain, thus most probably modulating or influencing the psychoactive effect of other molecules in cannabis (Navarro et al. 2018). CBN is mildly psychoactive, though there is usually little or no CBN in a fresh plant; it forms when THC degrades.

The psychoactive effects produced by the various component molecules—the proportions of which vary widely depending on the particular strain—and their synergetic interactions are still poorly understood. The complex chemistry of cannabis is reflected not only in the complex psychoactive effects of the plant resin but also in the wide range of possible effects on the body, organs and metabolism.

The ambivalent effects of cannabis

The effects of cannabis are complex, one of the important factors being the variant chemical constituents of the particular plant variety consumed (the plethora of which was discussed in a previous blog ‘Cannabis Plant Varieties’). It is generally understood that plants with proportionally high CBD content tend to induce relaxation and sedation, while those with high THC content are more stimulant in terms of mental activity.

Research has been conducted on the impact of cannabidiols (CBDs) on the effects of THCs; it seems that the combination of CBDs and THCs produces a different effect from either CBDs or THCs on their own. Although there is a general understanding that cannabidiols minimizes the onset and effects of THCs, it is apparent that the interactions of the different molecules is in fact more complex, as cannabidiols may enhance some of the effects of THCs, while at the same time diminishing other effects. Cannabidiols may increase the euphoria of THCs but limit sensations of anxiety and disordered thinking (Earlywine 2002:125).

Cannabis: both sedative and euphoriant

Thus, cannabis has the remarkable psychoactive property of being potentially either sedative or stimulating. Experienced users know that depending on prevailing mood, setting and the type and quantity of cannabis consumed, a dose may be soporific or stimulant; the experience may be ‘dreamy’ or a ‘clear high,’ or possibly a curious mixture of both. As regular users are familiar with, a dose of high-THC cannabis may keep one awake and unable to sleep, while on another occasion, in a different psychological state and using high-CBD, low-THC cannabis, it may be difficult to stay awake.

Besides the possible variant effects due to the chemistry of the cannabis plant consumed, another vital factor is dosage. Lee (2012:25) comments on the ‘biphasic’ activity of cannabis. Small doses may be most therapeutically effective; larger doses may be less so, even having a counteractive effect from that desired. This biphasic activity of cannabis not only applies to particular medical applications but also to other effects: for example, it has been observed that a low dose of THC-rich cannabis is usually aphrodisiac, whilst a high dose may have the opposite effect.

The complex effects of the compounds in cannabis are still being extensively researched. It is becoming apparent (Lee 2012:358ff.) that attempts by ‘Big Pharma’ to isolate particular molecules in the plant, and than market them to treat various mental and physical ailments, have in most instances not been particularly successful. Very often, unwanted side effects result from single-compound treatments. However, treatments using natural, ‘full-spectrum’ cannabis plants, which, depending on the strain used, may be rich in either THCs or CBDs and which contain other ‘counteractive’ compounds, are generally more effective and produce fewer, if any, unwanted side-effects.

References

Earlywine, Mitch (2002). Understanding Marijuana: A New Look at the Scientific

            Evidence. Oxford/New York: Oxford University Press.

ElSohly. Mahmoud, and Waseem Gul. ‘Constituents of Cannabis Sativa’. In Roger G.

            Pertwee (ed.), Handbook of Cannabis, pp. 3–22. Oxford: Oxford University

            Press.

Lee, Martin A. (2012). Smoke Signals: A Social History of Marijuana—Medical,

            Recreational, Scientific. New York/London/Toronto/Sydney/New Delhi:

            Scribner.

Navarro, Gemma, Irene Reyes-Resina, Verónica Sánchez de Medina, Rafael Rivas-

            Santisteban, Carolina Sánchez-Carnerero Callado, Fabrizio Vincenzi,

            Salvatore Casano, Carlos Ferreiro-Vera, Enric L. Canela, Pier Andrea Borea,

            Xavier Nadal, and Rafael Franco (2018). ‘Cannabigerol Action at

            Cannabinoid CB1–CB2 Heteroceptor Complexes’ Frontiers in Pharmacology,

            Vol. 9: 632, pp. 1–25. (accessed 17/05/2020)             https://www.frontiersin.org/articles/10.3389/fphar.2018.00632/full

Russo, Ethan B. (2007). ‘History of Cannabis and Its Preparation in Saga, Science,

            and Sobriquet’. Chemistry and Biodiversity, vol. 4, pp. 1614–1648.

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